The invention relates to reducing hair growth in mammals, particularly for cosmetic purposes.
A main function of mammalian hair is to provide environmental protection. However, that function has largely been lost in humans, in whom hair is kept or removed from various parts of the body essentially for cosmetic reasons. For example, it is generally preferred to have hair on the scalp but not on the face.
Various procedures have been employed to remove unwanted hair, including shaving, electrolysis, depilatory creams or lotions, waxing, plucking, and therapeutic anti androgens. These conventional procedures generally have drawbacks associated with them. Shaving, for instance, can cause nicks and cuts, and can leave a perception of an increase in the rate of hair regrowth. Shaving also can leave an undesirable stubble. Electrolysis, on the other hand, can keep a treated area free of hair for prolonged periods of time, but can be expensive, painful, and sometimes leaves scarring. Depilatory creams, though very effective, typically are not recommended for frequent use due to their high irritancy potential. Waxing and plucking can cause pain, discomfort, and poor removal of short hair. Finally, antiandrogens--which have been used to treat female hirsutism--can have unwanted side effects.
It has previously been disclosed that the rate and character of hair growth can be altered by applying to the skin inhibitors of certain enzymes. These inhibitors include inhibitors of 5-alpha reductase, omithine decarboxylase, S-adenosylmethionine decarboxylase, gamma-glutamyl transpeptidase, and transglutaminase. See, for example, Breuer et al., U.S. Pat. No. 4,885,289; Shander, U.S. Pat. No. 4,720,489; Ahluwalia, U.S. Pat. No. 5,095,007; Ahluwalia et al., U.S. Pat. No. 5,096,911; and Shander et al., U.S. Pat. No. 5,132,293.
Alkaline phosphatase is a widely distributed zinc-metalloenzyme that is thought to make a contribution to the maintenance of cellular homeostasis. Although the precise function for alkaline phosphatase in the maintenance of cellular homeostasis remains unclear, numerous physiological activities have been suggested for this enzyme. Such activities include controlling the levels of inorganic phosphate, regulation of inorganic phosphate transport, acting as a calcium-binding protein and a calcium-magnesium ATPase, and functioning as a tyrosine-specific phosphoprotein phosphatase.
In addition to its enzymatic activity, alkaline phosphatase levels have been used as diagnostic markers in the clinical evaluation of numerous diseases. For instance, alkaline phosphatase is used as a nonspecific indicator for cancer to characterize bone resorption patterns in individuals susceptible to osteoporosis.
Four alkaline phosphatase genes have been cloned and sequenced. In addition, their chromosomal locations have been determined and the regulation of these genes has been studied. Human alkaline phosphatases are encoded by a gene family including four loci. At the end of the long chromosome 2, bands q34-q37, are clustered three tissue specific alkaline phosphatase genes: intestinal, placental, and germ cell. A tissue nonspecific alkaline phosphatase gene is located at the end of the short arm of chromosome 1, bands p36.1-p34. The amino acid sequence homology for the tissue-specific enzymes is 90-98%, whereas the gnonspecific form is only 50-60% homologous with any of the specific forms.
Human alkaline phosphatase display a unique characteristic not seen in alkaline phosphatase from lower species (prokaryotic)--uncompetitive inhibition by certain L-amino acids (Millan, Clinica Chimica Acta. 209:123-129, 1992). For example, tryptophan, phenylalanine and leucine inhibit the tissue-specific form of alkaline phosphatase in a stereoselective fashion in that only the L-form is active. L-homoarginine acts as an inhibitor of the tissue nonspecific form of alkaline phosphatase in several species.
Inhibitors of mast cell degranulation interfere with the release of histamine from mast cells. Examples of inhibitors of mast cell degranulation include mycophenolic acid, bromoryptine, and cromoglycate.